Breast cancer is the second leading cause of cancer deaths among women in the United States. This year, nearly 200,000 people will be diagnosed with breast cancer (NCI, 2007). Another 41,000 will die from this devastating disease (NCI, 2007). Unfortunately, these statistics are increasing in the Western Hemisphere, even while mortality rates decline (Rovere et al., 2006). To date, only tamoxifen is FDA approved for the prevention of breast cancer in high risk individuals. However, many women hesitate to use this drug preventatively as the association of tamoxifen with increased risk of cervical and endometrial cancers, deep vein thrombosis and pulmonary emboli has been well established (Fisher B. et al., 1998;Rovere et al., 2006). Additionally, tamoxifen is only effective in one-third of breast cancer patients and after 5 years of therapy many patients develop tamoxifen-resistant tumors (Forbes JF, 1997;Fisher B et al., 1996). Therefore, there is an urgent need to explore new avenues in search of more promising chemopreventative agents. The Lumbee tribe, the 9th largest Native American Tribe in the nation, experience nearly half the incidence of breast cancer as their non-Hispanic and African American counterparts (NCMinority Health Facts, 2005). Yet, this population has never been investigated for cancer chemoprevention. Among the Lumbee certain medicinal and food plants are associated with cancer treatment and prevention. These include: Antirrhinum majus L. (Scrophulariaceae), Chimaphila maculata Pursh. (Pyrolaceae), Daucus carota L. (Apiaceae), Diospyros virginiana L. (Ebenaceae), Hydrastis canadensis L. (Ranunculaceae), Prunella vulgaris L. (Lamiaceae), and Brassica oleracea (Brassicaceae). The focus of this investigation will be on both food and medicinal plants associated with cancer chemoprevention among the Lumbee Tribe of North Carolina. The objective of the proposed work is to collect bulk samples of relevant plant species with our collaborators in Pembroke, North Carolina;identify and authenticate each plant species;prepare extracts of the collected plant material;perform bioassay guided fractionation;isolate biologically active compounds;and perform structure elucidation to determine the active chemical constituents. Bioassays to be employed include: estrogen receptor binding, and cytotoxicity assessment in breast cancer cell lines. The long-term goals of the project are the development of new and novel natural agents for the chemoprevention of breast cancer. Data generated from the proposed work will be used to further investigations in animal and human studies.